Evidence map›Paper›PMID 39746903›Full record

ArticleBone research2025

Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans.

Shishu Huang, Dashuang Gao, Zhenxia Li, Hongchen He, Xi Yu, Xuanhe You, Diwei Wu, Ze Du, Jiancheng Zeng, Xiaojun Shi and 12 more

Abstract read
In one paragraph

Article in Bone research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
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  3. Article
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  5. Transcriptomics in the Study of Bone and Cartilage.Current osteoporosis reports · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Shishu Huang *Department of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Dashuang Gao *The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.
Zhenxia Li *Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai, China.
Hongchen HeRehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
Xi YuRehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
Xuanhe YouDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Diwei WuDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Ze DuDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Jiancheng ZengDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Xiaojun ShiDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Qinshen HuDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Yong NieDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Zhong ZhangDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Zeyu LuoDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Duan WangDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Zhihe ZhaoState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Lingli LiDepartment of Nursing, West China Hospital, Sichuan University, Chengdu, China.
Guanglin WangDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.ORCID 0000-0002-6269-5704
Liping WangThe Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.ORCID 0000-0001-6893-3809
Zongke ZhouDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. zongke@126.com.ORCID 0000-0001-8091-0474
Di ChenResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. di.chen@siat.ac.cn.ORCID 0000-0002-4258-3457
Fan YangThe Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China. fan.yang@siat.ac.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81874027National Natural Science Foundation of China (National Science Foundation of China) T2394532, 82072489
6 · The paper itself

Abstract

Osteoarthritis (OA) is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms. Normal articular cartilage maintains at aneural state. Neuron guidance factor Semaphorin 3A (Sema3A) is a membrane-associated secreted protein with chemorepulsive properties for axons. However, the role of Sema3A in articular cartilage is still not clear. In the present studies, we investigated the functions of Sema3A in OA development in mice, non-human primates, and patients with OA. Sema3A has a protective effect on cartilage degradation, validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice. We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway. The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A, and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints. Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage, and could be potentially used for OA treatment.

Indexed as

Cartilage, ArticularChondrocytesHypertrophyNeuritesSemaphorin-3AAnimalsFemaleHaplorhiniHumansKnee JointMaleMiceMice, Inbred C57BLMice, KnockoutOsteoarthritis, KneeSemaphorin-3A

Identifiers

PMID39746903
PMCPMC11695747

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.